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Journal of Cosmetic Dermatology Jun 2019Glutathione is one of agents which is commonly used to lighten skin color in Asia as a dietary supplement. Previous studies suggest its potential effect of glutathione...
BACKGROUND
Glutathione is one of agents which is commonly used to lighten skin color in Asia as a dietary supplement. Previous studies suggest its potential effect of glutathione on skin color. However, the clinical efficacy of glutathione in oral form is still questionable due to its limited absorption and bioavailability.
AIM
To determine the clinical effects of glutathione on skin color and related skin conditions.
PATIENTS/METHODS
A systematic review was conducted using PubMed, CINAHL, Scopus, EMBASE and Cochrane library were searched from inceptions to October 2017. All clinical studies evaluating the effect of glutathione on any skin effects in healthy volunteer were included.
RESULTS
A total of four studies were included. Three studies were RCTs with placebo control, while one was a single-arm trial. One study used topical form, while others used oral form of glutathione with 250 to 500 mg/day. We found that both oral glutathione with the dosage of 500 mg/day and topical 2.0% oxidized glutathione could brighten skin color in sun-exposed area measured by skin melanin index. No significant differences in the reduction in skin melanin index were observed in sun-protected area for any products. In addition, glutathione also has a trend to improve skin wrinkle, skin elasticity, and UV spots. Some adverse events but nonserious were reported.
CONCLUSIONS
Current evidence of the skin whitening effect of glutathione is still inconclusive due to the quality of included studies and inconsistent findings. However, there is a trend that glutathione might brighten skin color at skin-exposed area.
Topics: Administration, Cutaneous; Administration, Oral; Biological Availability; Dietary Supplements; Glutathione; Humans; Melanins; Randomized Controlled Trials as Topic; Skin; Skin Absorption; Skin Lightening Preparations; Skin Pigmentation; Sunlight; Treatment Outcome
PubMed: 30895708
DOI: 10.1111/jocd.12910 -
Clinical Pharmacokinetics Aug 2022Metoprolol is recommended for therapeutic use in multiple cardiovascular conditions, thyroid crisis, and circumscribed choroidal hemangioma. A detailed systematic review...
BACKGROUND
Metoprolol is recommended for therapeutic use in multiple cardiovascular conditions, thyroid crisis, and circumscribed choroidal hemangioma. A detailed systematic review on the metoprolol literature would be beneficial to assess all pharmacokinetic parameters in humans and their respective effects on patients with hepatic, renal, and cardiovascular diseases. This review combines all the pharmacokinetic data on metoprolol from various accessible studies, which may assist in clinical decision making.
METHODOLOGY
The Google Scholar and PubMed databases were searched to screen articles associated with the clinical pharmacokinetics of metoprolol. The comprehensive literature search retrieved 41 articles including data on plasma concentration-time profiles after intravenous and oral (immediate-release, controlled-release, slow-release, or extended-release) routes of administration, and at least one pharmacokinetic parameter was reported in all studies included.
RESULTS
Out of 41 retrieved articles, six were after intravenous and 12 were after oral administration in healthy individuals. The oral studies depict a dose-dependent increase in maximum plasma concentration (C), time to reach maximum plasma concentration (T), and area under the concentration-time curve (AUC). Two studies were conducted in R- and S-enantiomers, in which one study reported the gender differences, depicting greater C and AUC among women, whereas in another study S-metoprolol was found to have higher values of C, T, and AUC in comparison with R-metoprolol. Results in different diseases depicted that after IV administration of 20 mg, patients with renal impairment showed an increase in clearance (CL) (60 L/h vs 48 L/h) compared with healthy subjects, whereas a decrease in CL (36.6 ± 7.8 L/h vs 48 ± 6.6 L/h) was seen in patients with hepatic cirrhosis at a similar dose. In comparison with a single oral dose following administration of 15 mg IV in three divided doses, patients having an acute myocardial infarction (AMI) showed an increase in C (823 nmol/L vs 248 nmol/L) at a steady state. Twenty different studies have reported significant changes in CL, C and AUC of metoprolol when it is co-administered with other drugs. One study has reported a drug-food interaction for metoprolol but no significant changes were seen in the C and AUC.
CONCLUSION
This review summarizes all the pharmacokinetic parameters of metoprolol after pooling up-to-date data from all the studies available. The summarized pharmacokinetic data presented in this review can assist in developing and evaluating pharmacokinetic models of metoprolol. Moreover, this data can provide practitioners with an insight into dosage adjustments among the diseased populations and can assist in preventing potential adverse drug reactions. This review can also help avoid side effects and drug-drug interactions.
Topics: Administration, Oral; Area Under Curve; Female; Food-Drug Interactions; Humans; Liver; Metoprolol
PubMed: 35764772
DOI: 10.1007/s40262-022-01145-y -
Nutrition Reviews Jan 2018Vitamin D is frequently prescribed as a supplement, yet its absorption remains poorly understood.
CONTEXT
Vitamin D is frequently prescribed as a supplement, yet its absorption remains poorly understood.
OBJECTIVE
This systematic review was performed to evaluate data on mechanisms involved in the intestinal absorption of vitamin D.
DATA SOURCES
PubMed, Embase, and Cochrane Library databases were searched.
STUDY SELECTION
The following studies were included: experimental laboratory studies of vitamin D absorption through the enterocyte brush-border membrane; absorption tests that used radiolabeled vitamin D; and clinical trials in adults that investigated a single dose of cholecalciferol or ergocalciferol and reported at least 2 measurements of serum cholecalciferol, ergocalciferol, or 25-hydroxyvitamin D.
DATA EXTRACTION
From 2069 articles identified, 46 met the inclusion criteria.
RESULTS
Different methods were employed to evaluate vitamin D absorption. Recent research suggests that vitamin D absorption is not an exclusive simple diffusion process. Vitamin D was better absorbed when it was consumed with fat-containing meals, but absorption also occurred without fat or oily vehicles. Factors that modified cholesterol absorption also altered vitamin D absorption.
CONCLUSION
Vitamin D is probably absorbed through passive diffusion and a mechanism involving membrane carriers, especially cholesterol transporters, although data remain scarce. Some data suggest that fat, when consumed concomitantly with vitamin D, improves vitamin D absorption.
Topics: Animals; Humans; Intestinal Absorption; Mice; Vitamin D
PubMed: 29025082
DOI: 10.1093/nutrit/nux034 -
Journal of Nanobiotechnology Jan 2024Exosomes are nanoscale extracellular vesicles secreted by cells and enclosed by a lipid bilayer membrane containing various biologically active cargoes such as proteins,... (Review)
Review
Exosomes are nanoscale extracellular vesicles secreted by cells and enclosed by a lipid bilayer membrane containing various biologically active cargoes such as proteins, lipids, and nucleic acids. Engineered exosomes generated through genetic modification of parent cells show promise as drug delivery vehicles, and they have been demonstrated to have great therapeutic potential for treating cancer, cardiovascular, neurological, and immune diseases, but systematic knowledge is lacking regarding optimization of drug loading and assessment of delivery efficacy. This review summarizes current approaches for engineering exosomes and evaluating their drug delivery effects, and current techniques for assessing exosome drug loading and release kinetics, cell targeting, biodistribution, pharmacokinetics, and therapeutic outcomes are critically examined. Additionally, this review synthesizes the latest applications of exosome engineering and drug delivery in clinical translation. The knowledge compiled in this review provides a framework for the rational design and rigorous assessment of exosomes as therapeutics. Continued advancement of robust characterization methods and reporting standards will accelerate the development of exosome engineering technologies and pave the way for clinical studies.
Topics: Humans; Exosomes; Tissue Distribution; Drug Delivery Systems; Extracellular Vesicles; Neoplasms; Pharmaceutical Preparations
PubMed: 38172932
DOI: 10.1186/s12951-023-02259-6 -
Lipids in Health and Disease Jan 2024Obstructive sleep apnea (OSA) has a bidirectional association with metabolic syndrome, and insulin resistance (IR). The triglyceride-glucose (TyG) index could be a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Obstructive sleep apnea (OSA) has a bidirectional association with metabolic syndrome, and insulin resistance (IR). The triglyceride-glucose (TyG) index could be a simply calculated marker of IR in OSA. However, its clinical application appears still limited. Hence, this systematic review and meta-analysis aimed to respond to this question by analyzing all the existing studies showing an association between OSA and the TyG index.
METHODS
Four online databases, including PubMed, Scopus, the Web of Science, and Embase were searched for studies evaluating the TyG index in OSA. After screening and data extraction, a random-effect meta-analysis was performed to compare the TyG index in OSA patients vs. healthy controls by calculating standardized mean difference (SMD) and 95% confidence interval (CI) and pooling the area under the curves (AUCs) for diagnosis of OSA based on this index.
RESULTS
Ten studies involving 16,726 individuals were included in the current systematic review. Meta-analysis indicated that there was a significantly higher TyG index in patients with OSA, compared with the healthy controls (SMD 0.856, 95% CI 0.579 to 1.132, P < 0.001). Also, TyG had a diagnostic ability for OSA representing a pooled AUC of 0.681 (95% CI 0.627 to 0.735). However, based on the two studies' findings, no difference between different severities of OSA was observed. Finally, our data showed that the TyG index is a good potential predictor of adverse outcomes in these patients.
CONCLUSION
Our study revealed that the TyG index is an easy-to-measure marker of IR for assessing OSA, both in diagnosis and prognosis. Our study supports its implementation in routine practice to help clinicians in decision-making and patient stratification.
Topics: Humans; Area Under Curve; Databases, Factual; Glucose; Insulin Resistance; Sleep Apnea, Obstructive; Triglycerides
PubMed: 38185682
DOI: 10.1186/s12944-024-02005-3 -
Frontiers in Endocrinology 2023The performance in evaluating thyroid nodules on ultrasound varies across different risk stratification systems, leading to inconsistency and uncertainty regarding... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The performance in evaluating thyroid nodules on ultrasound varies across different risk stratification systems, leading to inconsistency and uncertainty regarding diagnostic sensitivity, specificity, and accuracy.
OBJECTIVE
Comparing diagnostic performance of detecting thyroid cancer among distinct ultrasound risk stratification systems proposed in the last five years.
EVIDENCE ACQUISITION
Systematic search was conducted on PubMed, EMBASE, and Web of Science databases to find relevant research up to December 8, 2022, whose study contents contained elucidation of diagnostic performance of any one of the above ultrasound risk stratification systems (European Thyroid Imaging Reporting and Data System[Eu-TIRADS]; American College of Radiology TIRADS [ACR TIRADS]; Chinese version of TIRADS [C-TIRADS]; Computer-aided diagnosis system based on deep learning [S-Detect]). Based on golden diagnostic standard in histopathology and cytology, single meta-analysis was performed to obtain the optimal cut-off value for each system, and then network meta-analysis was conducted on the best risk stratification category in each system.
EVIDENCE SYNTHESIS
This network meta-analysis included 88 studies with a total of 59,304 nodules. The most accurate risk category thresholds were TR5 for Eu-TIRADS, TR5 for ACR TIRADS, TR4b and above for C-TIRADS, and possible malignancy for S-Detect. At the best thresholds, sensitivity of these systems ranged from 68% to 82% and specificity ranged from 71% to 81%. It identified the highest sensitivity for C-TIRADS TR4b and the highest specificity for ACR TIRADS TR5. However, sensitivity for ACR TIRADS TR5 was the lowest. The diagnostic odds ratio (DOR) and area under curve (AUC) were ranked first in C-TIRADS.
CONCLUSION
Among four ultrasound risk stratification options, this systemic review preliminarily proved that C-TIRADS possessed favorable diagnostic performance for thyroid nodules.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero, CRD42022382818.
Topics: Humans; Thyroid Nodule; Network Meta-Analysis; Thyroid Neoplasms; Area Under Curve
PubMed: 37720531
DOI: 10.3389/fendo.2023.1227339 -
Journal of Clinical Epidemiology Jun 2019The objective of this study was to compare performance of logistic regression (LR) with machine learning (ML) for clinical prediction modeling in the literature. (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVES
The objective of this study was to compare performance of logistic regression (LR) with machine learning (ML) for clinical prediction modeling in the literature.
STUDY DESIGN AND SETTING
We conducted a Medline literature search (1/2016 to 8/2017) and extracted comparisons between LR and ML models for binary outcomes.
RESULTS
We included 71 of 927 studies. The median sample size was 1,250 (range 72-3,994,872), with 19 predictors considered (range 5-563) and eight events per predictor (range 0.3-6,697). The most common ML methods were classification trees, random forests, artificial neural networks, and support vector machines. In 48 (68%) studies, we observed potential bias in the validation procedures. Sixty-four (90%) studies used the area under the receiver operating characteristic curve (AUC) to assess discrimination. Calibration was not addressed in 56 (79%) studies. We identified 282 comparisons between an LR and ML model (AUC range, 0.52-0.99). For 145 comparisons at low risk of bias, the difference in logit(AUC) between LR and ML was 0.00 (95% confidence interval, -0.18 to 0.18). For 137 comparisons at high risk of bias, logit(AUC) was 0.34 (0.20-0.47) higher for ML.
CONCLUSION
We found no evidence of superior performance of ML over LR. Improvements in methodology and reporting are needed for studies that compare modeling algorithms.
Topics: Algorithms; Area Under Curve; Humans; Logistic Models; Models, Theoretical; Outcome Assessment, Health Care; Predictive Value of Tests; Sensitivity and Specificity; Supervised Machine Learning
PubMed: 30763612
DOI: 10.1016/j.jclinepi.2019.02.004 -
European Journal of Drug Metabolism and... Jul 2021Short bowel syndrome is a clinical condition defined by malabsorption of nutrients and micronutrients, most commonly following extensive intestinal resection. Due to a...
BACKGROUND AND OBJECTIVES
Short bowel syndrome is a clinical condition defined by malabsorption of nutrients and micronutrients, most commonly following extensive intestinal resection. Due to a loss of absorptive surfaces, the absorption of orally administered drugs is also often affected. The purpose of this study was to systematically review the published literature and examine the effects of short bowel syndrome on drug pharmacokinetics and clinical outcomes.
METHODS
Studies were identified through searches of databases MEDLINE, EMBASE, Web of Science, and SCOPUS, in addition to hand searches of studies' reference lists. Two reviewers independently assessed studies for inclusion, yielding 50 studies involving 37 different drugs in patients with short bowel syndrome.
RESULTS
Evidence of decreased drug absorption was observed in 29 out of 37 drugs, 6 of which lost therapeutic effect, and 14 of which continued to demonstrate clinical benefit through drug monitoring.
CONCLUSIONS
The influence of short bowel syndrome on drug absorption appears to be drug-specific and dependent on the location and extent of resection. The presence of a colon in continuity may also influence drug bioavailability as it can contribute significantly to the absorption of drugs (e.g., metoprolol); likewise, drugs that have a wide absorption window or are known to be absorbed in the colon are least likely to be malabsorbed. Individualized dosing may be necessary to achieve therapeutic efficacy, and therapeutic drug monitoring, where available, should be considered in short bowel syndrome patients, especially for drugs with narrow therapeutic indices.
Topics: Administration, Oral; Biological Availability; Humans; Intestinal Absorption; Pharmaceutical Preparations; Pharmacokinetics; Short Bowel Syndrome
PubMed: 34196913
DOI: 10.1007/s13318-021-00696-y -
Pharmacological Reports : PR Apr 2016The number of newly approved generic psychotropic drugs increases every year and, in many countries, their sales exceed the sales of brand-name counterparts. In order... (Review)
Review
The number of newly approved generic psychotropic drugs increases every year and, in many countries, their sales exceed the sales of brand-name counterparts. In order for any generic drug to receive an approval of regulatory authorities, its bioequivalence with the corresponding reference product must be demonstrated. Moreover, generic drugs must meet the same quality standards as reference drugs. However, many psychiatrists express concerns about use of generic drugs. We carried out a systematic analysis of the relevant literature indexed in PubMed and Cochrane databases. The MeSH term "generic" was combined with terms describing antipsychotic and antidepressive drugs, including their pharmaceutical names and relevant mental disorders. All 26 articles including either clinical studies or case reports have been qualified for a detailed analysis. No cases describing switches between two generics were found. Therapeutic equivalence studies evaluating antipsychotics included clozapine, olanzapine, and risperidone. The clinical status was judged to have worsened in 15.7% patients treated with clozapine. The number of relapses before and after the switch was not significantly different in patients treated with olanzapine. Two case reports showed clinical state deterioration after switch to generic risperidone. The clinical outcome after conversion to a generic antidepressant was evaluated only in one retrospective study. That study analyzed the outcomes of treatment with citalopram and revealed mental state deterioration in 11.6% of patients. Only single reports describe cases of impaired efficacy or adverse events after the switch to a generic antidepressant, including fluoxetine, mirtazapine, and venlafaxine. No cases of suicidal attempt after the switch were reported. Although the overall number of described cases is rather modest, health professionals should be aware of possible changes in the therapeutic effectiveness after changing to a generic medicine.
Topics: Antidepressive Agents; Antipsychotic Agents; Clinical Studies as Topic; Drugs, Generic; Humans; Retrospective Studies; Therapeutic Equivalency
PubMed: 26922520
DOI: 10.1016/j.pharep.2015.08.017 -
Expert Review of Clinical Pharmacology Jun 2018This article includes a combined analysis of therapeutic drug monitoring (TDM) studies and a review of the marketer's data on pharmacological mechanisms. Areas covered:... (Review)
Review
This article includes a combined analysis of therapeutic drug monitoring (TDM) studies and a review of the marketer's data on pharmacological mechanisms. Areas covered: An article search led to the inclusion of 21 paliperidone studies in the systematic review plus 2 case reports. Paliperidone clearance was calculated from: 1) steady-state studies using concentration/dose (C/D) ratios, and 2) single-dose studies describing 24-h area under the curve calculations. The marketed extended-release formulation has 28% bioavailability. Calculated mean C/D ratios (ng/ml/mg/d) were: 1) 4.09 in 6 studies of 221 non-Korean and non-geriatric adult patients, 2) 2.59 in 2 studies of 100 Korean adult patients, and 3) 6.89 in 1 study with 15 elderly Japanese patients. The limited drug-drug interaction studies indicated that carbamazepine is a clinically relevant inducer requiring three times the dosage, and that valproate, probably an inhibitor, requires half the dosage. Renal impairment markedly decreased paliperidone elimination, and other antipsychotics should be considered. Expert Commentary: We recommend more use of: 1) paliperidone TDM in clinical practice, 2) TDM when moving from oral to long-acting paliperidone, 3) better designs for paliperidone TDM studies, 4) laboratory studies on paliperidone pharmacokinetic mechanisms, and 5) TDM studies comparing paliperidone and risperidone dosing.
Topics: Administration, Oral; Adult; Aged; Antipsychotic Agents; Area Under Curve; Biological Availability; Delayed-Action Preparations; Drug Interactions; Drug Monitoring; Humans; Paliperidone Palmitate; Risperidone
PubMed: 29776316
DOI: 10.1080/17512433.2018.1478727